This invention relates generally to a method and apparatus for controlling liquid flow through nanoscale capillary tubing and channels, by freezing the liquid or thawing the frozen liquid in a segment of the tube or channel.
The management of the flow of liquids within small diameter channels presents challenges as the scale of the channels and volumes of the liquids are reduced. One significant constraint is the configuration of traditional valve technology. Nanoliter volume-scale fluid management is severely negatively affected by poorly-swept or xe2x80x9cdeadxe2x80x9d volume that is inherent within traditional valving methods. The method of using a fluid within these nanoscale capillaries and channels to act as its own on/off valve by freezing and thawing that liquid is known in the art, see for example U.S. Pat. Nos. 6,159,744 and 5,795,788. It has been found that the flow of liquids can be diverted to a further channel or chamber by merely freezing and thawing the liquid contained within a segment of tubing or channel. This flow-switching device, that is commonly referred to as xe2x80x9cfreeze thaw valvingxe2x80x9d, requires no moving parts and most importantly contributes substantially no dead volume within the analytical system.
Prior art freeze thaw valves rely on the resistance to shearing motion that is obtained between a resulting frozen plug and the channel wall to restrict fluid flow during the valve closed state. While this method of fluid management has been successful in analytical systems involving low pressure, experience with these valves at high pressures (e.g. greater than 20,000 p.s.i) reveals that the frozen plug can be displaced from the valving segment resulting in low-level flow or leakage. As the frozen plug is extruded out of the valving segment, new fluid entering the valving segment is solidified maintaining an incomplete valve closure. Unfortunately, this low-level leakage is unacceptable when these freeze thaw valves are used for capillary chromatography and other nanoscale analytical systems where fluid flow rates as low as a few nanoliters per minute and high delivery pressures are used.
The invention provides methods and devices for the management of fluid flow within high pressure nanoscale analytical systems. The device comprises freeze thaw valves implemented by fluid conduits having differing geometries to restrain the motion of frozen plugs. The freeze thaw valve contemplated by the invention is directed to use in high-pressure analytical systems. The geometry of a fluid conduit within a freeze thaw segment of the valve is configured to cause constriction of at least a portion of a freeze plug, when a hydraulic load is applied to the upstream side of the plug. This geometry is used in the flow path of the freeze thaw valve segment to prevent movement of the frozen plug at high pressures to substantially avoid leakage. The configuration of the freeze thaw segment can be a variety of geometries that cause the constriction of the freeze plug when a hydraulic load is applied.
The fluid conduits contemplated within the invention have transverse dimensions (normal to the flow axis) on the order of approximately 2 xcexcm to 500 xcexcm, and more typically 25-100 xcexcm. The pressures within the analytical systems utilizing the freeze thaw segments contemplated within the invention are on the order of approximately 20,000 PSIG or greater.
Means for freezing the liquid phase within the freeze thaw segment, in an illustrative embodiment, is a finely directed jet of cooling gas. The cooling gas can be provided from a liquefied source of gas under pressure, such as liquid carbon dioxide. Alternative means for freezing the liquid phase, within the freeze thaw segment, include the use of a cryogenic liquid such as liquid nitrogen, or a thermoelectric method such as a Peltier-based heat pump. It is contemplated within the invention, that a warming means for thawing the frozen plug, within the freeze thaw segment, can be a directed jet of warm air or other gas, an electrical resistance heating element, or the ambient air within the analytical environment. The temperature of the freeze thaw segment may be monitored by conventional means known to those skilled in the art such as a thermocouple incorporated into the freeze thaw segment. Further, the cooling means may be applied continuously during the time required to maintain the limiting frozen plug and interrupted by alternative heating means when fluid flow is desired.
Advantages of the invention include provision of a simple and low cost mechanism for implementing freeze thaw valving in high pressure contexts. Migration of the frozen plug and leakage are substantially avoided. The present invention provides methods and apparatus for the management of fluid flow within a nanoscale high pressure analytical system while avoiding introduction of poorly-swept or dead volumes.